Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.

BACKGROUND AND OBJECTIVE: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

Diagnostic performance of CT with Valsalva maneuver for the diagnosis and characterization of inguinal hernias.

PURPOSE: Inguinal hernias are mainly diagnosed clinically, but imaging can aid in equivocal cases or for treatment planning. The purpose of this study was to evaluate the diagnostic performance of CT with Valsalva maneuver for the diagnosis and characterization of inguinal hernias. METHODS: This single-center retrospective study reviewed all consecutive Valsalva-CT studies between 2018 and 2019. A composite clinical reference standard including surgery was used. Three blinded, independent readers (readers 1-3) reviewed the CT images and scored the presence and type of inguinal hernia. A fourth reader measured hernia size. Interreader agreement was quantified with Krippendorff's α coefficients. Sensitivity, specificity, and accuracy of Valsalva-CT for the detection of inguinal hernias was computed for each reader. RESULTS: The final study population included 351 patients (99 women) with median age 52.2 years (interquartile range (IQR), 47.2, 68.9). A total of 381 inguinal hernias were present in 221 patients. Sensitivity, specificity, and accuracy were 85.8%, 98.1%, and 91.5% for reader 1, 72.7%, 92.5%, and 81.8% for reader 2, and 68.2%, 96.3%, and 81.1% for reader 3. Hernia neck size was significantly larger in cases correctly detected by all three readers (19.0 mm, IQR 13, 25), compared to those missed by all readers (7.0 mm, IQR, 5, 9; p < 0.001). Interreader agreement was substantial (α = 0.723) for the diagnosis of hernia and moderate (α = 0.522) for the type of hernia. CONCLUSION: Valsalva-CT shows very high specificity and high accuracy for the diagnosis of inguinal hernia. Sensitivity is only moderate which is associated with missed smaller hernias.

[Healthcare cost reimbursement without application-Experiences of a German bariatric service]. / Kostenübernahme bariatrischer Operationen ohne Antragstellung ­ Erfahrungen in einem deutschen Adipositaszentrum.

BACKGROUND: Only a small proportion of patients with morbid obesity in Germany have access to the currently most effective treatment, bariatric surgery. A major reason for this is the restrictive attitude of health insurance companies regarding the reimbursement of costs. OBJECTIVE: To record the postoperative rate of cost coverage by health insurance companies without the currently common preoperative application for morbidly obese patients who received a guideline-indicated bariatric surgery. METHODS: The process of postoperative reimbursement was evaluated through a prospective database over a 2-year period. Cases of primary reimbursement were correlated with respect to age, BMI, comorbidities and membership of a specific health insurance company. Rejected coverage cases were followed up for further advocacy and social court process. RESULTS: A total of 188 patients underwent bariatric surgery as indicated in the guidelines without prior application. Primary cost coverage was achieved in 76.6% (n = 144). There was no correlation with BMI, comorbidities or health insurance affiliation. Patients over 40 years of age were significantly more likely to be covered for costs. For patients without postoperative cost coverage, an out of court settlement was reached in 7 cases, 8 cases were heard by the social courts and 29 cases were still being processed by lawyers. CONCLUSION: Despite the relatively high rate of primary cost coverage, this analysis also shows the restrictive attitude of the health insurance companies regarding bariatric surgery with corresponding economic pressure on the service providers. The consistent implementation of application-free surgery seems necessary to increase the political pressure on health insurers and social courts.

Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy: 5-year outcomes of merged data from two randomized clinical trials (SLEEVEPASS and SM-BOSS).

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) are both effective surgical procedures to achieve weight reduction in patients with obesity. The trial objective was to merge individual-patient data from two RCTs to compare outcomes after LSG and LRYGB. METHODS: Five-year outcomes of the Finnish SLEEVEPASS and Swiss SM-BOSS RCTs comparing LSG with LRYGB were analysed. Both original trials were designed to evaluate weight loss. Additional patient-level data on type 2 diabetes (T2DM), obstructive sleep apnoea, and complications were retrieved. The primary outcome was percentage excess BMI loss (%EBMIL). Secondary predefined outcomes in both trials included total weight loss, remission of co-morbidities, improvement in quality of life (QoL), and overall morbidity. RESULTS: At baseline, 228 LSG and 229 LRYGB procedures were performed. Five-year follow-up was available for 199 of 228 patients (87.3 per cent) after LSG and 199 of 229 (87.1 per cent) after LRYGB. Model-based mean estimate of %EBMIL was 7.0 (95 per cent c.i. 3.5 to 10.5) percentage points better after LRYGB than after LSG  (62.7 versus 55.5 per cent respectively; P < 0.001). There was no difference in remission of T2DM, obstructive sleep apnoea or QoL improvement; remission for hypertension was better after LRYGB compared with LSG (60.3 versus 44.9 per cent; P = 0.049). The complication rate was higher after LRYGB than LSG (37.2 versus 22.5 per cent; P = 0.001), but there was no difference in mean Comprehensive Complication Index value (30.6 versus 31.0 points; P = 0.859). CONCLUSION: Although LRYGB induced greater weight loss and better amelioration of hypertension than LSG, there was no difference in remission of T2DM, obstructive sleep apnoea, or QoL at 5 years. There were more complications after LRYGB, but the individual burden for patients with complications was similar after both operations.

Alterations in energy expenditure in Roux-en-Y gastric bypass rats persist at thermoneutrality.

BACKGROUND: The compensatory decrease in energy expenditure (EE) in response to body weight loss is attenuated by Roux-en-Y gastric bypass (RYGB) surgery in rats. The thermoneutral zone (TNZ) is at higher temperatures in rodents than in humans. Consequently, rodents may be under moderate cold stress if EE is measured at room temperature, leading to increased EE due to adaptive thermogenesis. We speculated that the reported alterations in EE of RYGB rats at room temperature are caused by higher adaptive thermogenesis and are therefore not present at thermoneutrality. METHODS: Male Wistar rats were randomized for RYGB or sham surgery. Some sham rats were body weight matched (BWM) to the RYGB rats by food restriction, the others received ad libitum access to food (AL). EE, body temperature, physical activity and food intake were measured at ambient temperatures between 22 and 32 °C to determine the TNZ. Adaptive thermogenesis requires ß3-adrenergic receptor-mediated uncoupling protein-1 (UCP-1) expression in brown adipose tissue (BAT). The in vivo thermogenic capacity of BAT was determined by administering the ß3-adrenergic agonist CL316,243, and UCP-1 protein expression was measured at room temperature. RESULTS: The TNZ was between 28 and 30 °C for AL and RYGB and between 30 and 32 °C for BWM rats, respectively. In contrast to AL and BWM rats, EE was not significantly higher at room temperature than at thermoneutrality in RYGB rats, reflecting a lack of adaptive thermogenesis. Consistently, both the thermogenic capacity of BAT and UCP-1 expression were decreased in RYGB compared with AL rats at room temperature. CONCLUSIONS: Our data confirm that the decrease in EE after body weight loss is attenuated by RYGB surgery and show that this effect persists at thermoneutrality. Contrary to our hypothesis, we found that adaptive thermogenesis at room temperature is reduced in RYGB rats.

[Surgery as pluripotent instrument for metabolic disease. What are the mechanisms?]. / Chirurgie als pluripotentes Instrument gegen eine metabolische Erkrankung : Was sind die Mechanismen?

Bariatric metabolic surgery currently offers the most effective treatment to achieve sustained weight loss and improvement in metabolic comorbidities, such as type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. The number of cases performed in Germany and also worldwide is continuously increasing but the underlying mechanisms of bariatric metabolic surgery are still not completely elucidated. Roux-en-Y gastric bypass (RYGB) surgery represents one of the most commonly used and therefore most frequently investigated bariatric metabolic procedures. Traditionally, its effectiveness was attributed to food restriction and malabsorption but in the meantime it has become evident that the underlying postoperative mechanisms of RYGB seem to be much more complex. Potential mechanisms include multiple physiological changes, such as altered levels of gastrointestinal hormones, increased energy expenditure and modified gut microbiota as well as many other factors. This review article therefore aims to offer an up to date overview of relevant mechanisms that improve obesity and its associated comorbidities after RYGB surgery.

Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery.

BACKGROUND: Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery. METHODS: Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. RESULTS: Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg (P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg (P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 µmol/L (P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 µmol/L (P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant (P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO. CONCLUSIONS: After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO-ADMA axis. Other causes for the changes in BP should therefore be considered.

Roux-en-Y gastric bypass in mice--surgical technique and characterisation.

BACKGROUND: A reproducible Roux-en-Y gastric bypass (RYGB) model in mice is needed to study the physiological alterations after surgery. METHODS: Male C57BL6 mice weighing 29.0 ± 0.8 g underwent either RYGB (n = 14) or sham operations (n = 6). RYGB surgery consisted of a small gastric pouch (~2 % of the initial stomach size), a biliopancreatic and alimentary limb of 10 cm each and a common channel of 15 cm. Animals had free access to standard chow in the postoperative period. Body mass and food intake were recorded for 60 days. Bomb calorimetry was used for faecal analysis. Anatomical rearrangement was assessed using planar X-ray fluoroscopy and computed tomography (CT) after oral Gastrografin® injection. RESULTS: RYGB surgery led to a sustained reduction in body weight compared to sham-operated mice (postoperative week 1: sham 27.8 ± 0.7 g vs. RYGB 26.5 ± 1.0 g, p = 0.008; postoperative week 8: sham 30.7 ± 0.8 g vs. RYGB 28.4 ± 1.1 g, p = 0.003). RYGB mice ate less compared to shams (sham 4.6 ± 0.2 g/day vs. RYGB 4.3 ± 0.4 g/day, p < 0.001). There were no differences in faecal mass (p = 0.13) and faecal energy content (p = 0.44) between RYGB and shams. CT scan demonstrated the expected anatomical rearrangement without leakage or stenosis. Fluoroscopy revealed rapid pouch emptying. CONCLUSIONS: RYGB with a small gastric pouch is technically feasible in mice. With this model in place, genetically manipulated mouse models could be used to study the physiological mechanisms involved with metabolic changes after gastric bypass.

Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass.

BACKGROUND: Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandial gut hormone response in comparison with patients who lost an adequate amount of BW. The effects of additional gut hormone administration after gastric bypass are unknown. METHODS: The effects of peripheral administration of peptide YY3-36 (PYY3-36; 300 nmol kg(-1)), glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (20 nmol kg(-1)) and somatostatin analogue octreotide (10 µg kg(-1)) on feeding and BW were evaluated in rats after gastric bypass. RESULTS: Gastric bypass rats weighed (P<0.01) and ate less on postoperative day 5 (P<0.001) and thereafter, whereas postprandial plasma PYY and GLP-1 levels were higher compared with sham-operated controls (P<0.001). Administration of both PYY3-36 and Exendin-4 led to a further decrease in food intake in bypass rats compared with saline treatment (P=0.02 and P<0.0001, respectively). Similar reduction in food intake was observed in sham rats (P=0.02 and P<0.001, respectively). Exendin-4 treatment resulted in a significant BW loss in bypass (P=0.03) and sham rats (P=0.04). Subsequent treatment with octreotide led to an increase in food intake in bypass (P=0.007), but not in sham rats (P=0.87). CONCLUSION: Peripheral administration of PYY3-36 and Exendin-4 reduces short-term food intake, whereas octreotide increases short-term food intake in rats after gastric bypass. The endogenous gut hormone response after gastric bypass can thus potentially be further enhanced by additional exogenous therapy with pharmacological doses of gut hormones in patients with insufficient weight loss or weight regain after surgery.

Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation.

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30 µg/kg), agonist exendin-4 (1 µg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.

Changes in eating behaviour and meal pattern following Roux-en-Y gastric bypass.

BACKGROUND: Little is known about eating behaviour and meal pattern subsequent to Roux-en-Y gastric bypass (RYGB), knowledge important for the nutritional care process. The objective of the study was to obtain basic information of how meal size, eating rate, meal frequency and eating behaviour change upon the RYGB surgery. MATERIALS AND METHODS: Voluntary chosen meal size and eating rate were measured in a longitudinal, within subject, cohort study of 43 patients, 31 women and 12 men, age 42.6 (s.d. 9.7) years, body mass index (BMI) 44.5 (4.9) kg m(-2). Thirty-one non-obese subjects, 37.8 (13.6) years, BMI 23.7 (2.7) kg m(-2) served as a reference group. All subjects completed a meal pattern questionnaire and the Three-Factor Eating Questionnaire (TFEQ-R21). RESULTS: Six weeks postoperatively meal size was 42% of the preoperative meal size, (P<0.001). After 1 and 2 years, meal size increased but was still lower than preoperative size 57% (P<0.001) and 66% (P<0.001), respectively. Mean meal duration was constant before and after surgery. Mean eating rate measured as amount consumed food per minute was 45% of preoperative eating rate 6 weeks postoperatively (P<0.001). After 1 and 2 years, eating rate increased to 65% (P<0.001) and 72% (P<0.001), respectively, of preoperative rate. Number of meals per day increased from 4.9 (95% confidence interval, 4.4,5.4) preoperatively to 6 weeks: 5.2 (4.9,5.6), (not significant), 1 year 5.8 (5.5,6.1), (P=0.003), and 2 years 5.4 (5.1,5.7), (not significant). Emotional and uncontrolled eating were significantly decreased postoperatively, (both P<0.001 at all-time points), while cognitive restraint was only transiently increased 6 weeks postoperatively (P=0.011). CONCLUSIONS: Subsequent to RYGB, patients display markedly changed eating behaviour and meal patterns, which may lead to sustained weight loss.

Gastrointestinal hormones, energy balance and bariatric surgery.

Despite increasing understanding of the changes in gastrointestinal and central neuroendocrine signaling following gastric bypass surgery (GBP) in morbidly obese patients, the mechanisms underlying weight loss and weight loss maintenance are not completely understood. Changes in energy expenditure are increasingly recognized as an important factor contributing to weight loss and metabolic effects in patients following GBP surgery. Experimental data regarding changes in energy balance following metabolic surgery in animal models suggest increased energy expenditure postoperatively as an important factor in the process of weight loss. However, the underlying neuroendocrine mechanisms are not well understood, and data regarding changes in energy expenditure in humans after GBP are inconsistent because of heterogenic patient populations and variable techniques. Nevertheless, a growing body of knowledge and understanding of the complex entero-neurohumoral interaction with its consequences in appetite, satiety and energy expenditure will help reveal the mechanisms of weight loss and weight loss maintenance following GBP surgery. Here we review how gastrointestinal hormones potentially regulate energy balance, and summarize current available experimental and clinical data on energy expenditure following obesity surgery.

Alterations of sucrose preference after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass.

Could the mechanisms of bariatric surgery hold the key for novel therapies? report from a Pennington Scientific Symposium.

Bariatric surgery is the most effective method for promoting dramatic and durable weight loss in morbidly obese subjects. Furthermore, type 2 diabetes is resolved in over 80% of patients. The mechanisms behind the amelioration in metabolic abnormalities are largely unknown but may be due to changes in energy metabolism, gut peptides and food preference. The goal of this meeting was to review the latest research to better understand the mechanisms behind the 'magic' of bariatric surgery. Replication of these effects in a non-surgical manner remains one of the ultimate challenges for the treatment of obesity and diabetes. Promising data on energy metabolism, gastrointestinal physiology, hedonic response and food intake were reviewed and discussed.

Diabetes resolution and hyperinsulinaemia after metabolic Roux-en-Y gastric bypass.

The global prevalence of type 2 diabetes mellitus and impaired glucose metabolism continues to rise in conjunction with the pandemic of obesity. The metabolic Roux-en-Y gastric bypass operation offers the successful resolution of diabetes in addition to sustained weight loss and excellent long-term outcomes in morbidly obese individuals. The procedure consists of the physiological BRAVE effects: (i) Bile flow alteration; (ii) Reduction of gastric size; (iii) Anatomical gut rearrangement and altered flow of nutrients; (iv) Vagal manipulation and (v) Enteric gut hormone modulation. This operation provides anti-diabetic effects through decreasing insulin resistance and increasing the efficiency of insulin secretion. These metabolic outcomes are achieved through weight-independent and weight-dependent mechanisms. These include the foregut, midgut and hindgut mechanisms, decreased inflammation, fat, adipokine and bile metabolism, metabolic modulation, shifts in gut microbial composition and intestinal gluconeogenesis. In a small minority of patients, gastric bypass results in hyperinsulinaemic hypoglycaemia that may lead to nesidioblastosis (pancreatic beta-cell hypertrophy with islet hyperplasia). Elucidating the precise metabolic mechanisms of diabetes resolution and hyperinsulinaemia after surgery can lead to improved operations and disease-specific procedures including 'diabetes surgery'. It can also improve our understanding of diabetes pathogenesis that may provide novel strategies for the management of metabolic syndrome and impaired glucose metabolism.

Renal cytokines improve early after bariatric surgery.

BACKGROUND: Bariatric surgery has been suggested to improve arterial hypertension and renal function. This prospective controlled observational study aimed to investigate changes in renal inflammation, renal function and arterial blood pressure before and after bariatric surgery. METHODS: Blood pressure was measured, and urine and blood samples were collected from 34 morbidly obese patients before and 4 weeks after bariatric surgery. Serum levels of cystatin C, creatinine, albumin, cholesterol and C-reactive protein (CRP) were measured, along with urinary cytokine/creatinine ratios for macrophage migration inhibitory factor (MIF), monocyte chemotactic protein (MCP) 1, chemokine ligand (CCL) 18 and CCL-15. RESULTS: Mean(s.e.m.) bodyweight dropped from 124·1(2·6) to 114·8(2·4) kg (P < 0·001) and mean arterial blood pressure decreased from 105·7(1·8) to 95·5(1·2) mmHg (P < 0·001) in 4 weeks. Systemic and urinary inflammatory markers improved, with a reduction in serum CRP level (P < 0·001), and decreased urinary MIF/creatinine (P < 0·001), MCP-1/creatinine (P < 0·001) and CCL-18/creatinine (P = 0·003) ratios. In contrast, urinary CCL-15/creatinine ratios did not change and the glomerular filtration rate, measured by serum cystatin C, was unchanged (P = 0·615). CONCLUSION: Surgically induced weight loss contributed to a decrease in blood pressure and markers of renal inflammation. The reduced levels of CRP and urinary cytokines suggest that bariatric surgery attenuates systemic and renal inflammatory status.

[Comment on the article "Operative Techniques and Outcomes in Metabolic Surgery: Sleeve Gastrectomy"]. / Kommentar zum Artikel "Operative Techniken und deren Outcome in der metabolischen Chirurgie: Sleeve-Gastrektomie" von T.P.Hüttl et al.

The review article "Operative Techniques and Outcomes in Metabolic Surgery: Sleeve Gastrectomy" by Hüttl et al. is concerned with laparoscopic sleeve stomach operations ("sleeve gastrectomy") for the surgical treatment of morbid obesity (Zentralblatt für Chirurgie 2009; 134: 24-31). After an analysis of the available literature and own results, the authors concluded that the laparoscopic sleeve operation is established today as an effective standard procedure in the therapy for obesity.We would like to comment on the content of this article.

[Why patients lose weight after bariatric operations]. / Warum Patienten nach bariatrischen Operationen Gewicht abnehmen.

The obesity epidemic is in Germany as well as worldwide a major health problem which is associated with increased morbidity and mortality. Bariatric surgery is currently the most effective therapy for significant and sustained weight loss. The most common form of bariatric surgery worldwide is Roux-en-Y gastric bypass surgery. The underlying mechanisms behind the superiority of this procedure are unclear and remain to be elucidated, but recent findings suggest that gastrointestinal hormones play an important role rather than malabsorption or restriction. It appears that gastric bypass surgery alters the physiology of weight regulation and eating behaviour in patients who have undergone the procedure. Gastrointestinal hormones have recently been found to be an important element in the physiology of appetite regulation due to the signals from the periphery to the brain. It is the purpose of this article to review the current knowledge about the regulation of body weight and eating behaviour by gastrointestinal hormones and how their levels are altered after bariatric surgery.

Metabolic surgery: an evolution through bariatric animal models.

Metabolic surgery was developed through the application and experience gained from bariatric or weight loss procedures. Much of our knowledge from the procedures comes from the study of animal models, where they have revealed anatomic feasibility, systemic physiological elements and cellular metabolic effects. The first generation of operation included the jejunoileal bypass and partial ileal bypass that led to the development of the current procedures including Roux-en-Y gastric bypass, biliopancreatic diversion, adjustable gastric banding and sleeve gastrectomy. These operations carry significant metabolic benefits and can reduce the risk of diabetes, heart disease and cancer. Further insights from these animal models can reveal genetic, molecular and systemic effects that can enhance and develop the next generation of metabolic operations.

Tumor cell dissemination in a human colon cancer animal model: orthotopic implantation or intraportal injection?

BACKGROUND: The development of therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models generating both metastases and the dissemination of tumor cells. METHODS: To prove the efficiency of orthotopic implantation concerning induction of minimal residual disease (MRD) colorectal cancer tissue from 10 patients was transplanted orthotopically into nude mice. In the intraportal injection model 1 x 10(6) HT-29 human colon cancer cells were injected. We investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human colon cancer cells in bone marrow. RESULTS: Following orthotopic implantation of human colon cancer tissue the lymph node and hepatic metastasis rates were low. MRD as reflected by CK-20 positivity of the bone marrow was present in 22.2%. The intraportal injection of 1 x 10(6) HT-29 human colon cancer cells produced hepatic metastases in up to 89% of all animals. The intraportal injection of 1 x 10(6) cells also generated MRD in the bone marrow in 63% of animals. CONCLUSIONS: The intraportal injection model represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and MRD in the bone marrow. In this regard it seems to be superior to the orthotopic implantation model.